Major depressive disorder is a leading cause of disability worldwide, affecting approximately 280 million people. While psychotherapy is effective for many patients, pharmacotherapy with antidepressants is a cornerstone of treatment, especially for moderate-to-severe depression.

Selective serotonin reuptake inhibitors (SSRIs) — sertraline, escitalopram, fluoxetine, citalopram, paroxetine — are the most commonly prescribed antidepressants. They work by blocking the reuptake of serotonin in the synaptic cleft, increasing serotonin availability. SSRIs are preferred as first-line therapy due to their favorable side effect profile, safety in overdose, and broad efficacy across anxiety and depressive disorders.

Initial side effects often include nausea, headache, insomnia or drowsiness, and increased anxiety — these typically resolve within 1–2 weeks. Sexual dysfunction (decreased libido, delayed orgasm) affects 30–50% of patients and may persist. Weight changes are variable — fluoxetine tends to be weight-neutral, while paroxetine may cause weight gain.

Serotonin-norepinephrine reuptake inhibitors (venlafaxine, duloxetine, desvenlafaxine) block reuptake of both serotonin and norepinephrine. They may be more effective for patients with concurrent chronic pain conditions (duloxetine is also approved for diabetic neuropathy and fibromyalgia). Additional side effects compared to SSRIs include elevated blood pressure (especially with venlafaxine at higher doses) and more prominent discontinuation symptoms.

Bupropion (an NDRI) is notable for its activating profile and lack of sexual side effects, making it a good option for patients bothered by SSRI-related sexual dysfunction. Mirtazapine (NaSSA) is sedating and appetite-stimulating, useful for patients with insomnia and poor appetite. Tricyclic antidepressants (amitriptyline, nortriptyline) remain effective but carry more side effects and overdose risk. MAO inhibitors are rarely used today due to dietary restrictions and drug interactions.

Antidepressants typically take 2–4 weeks to show clinical benefit, with full effect at 6–8 weeks. This delay is one of the biggest challenges in treatment, as patients may discontinue prematurely. If the first antidepressant is ineffective after an adequate trial (6–8 weeks at therapeutic dose), switching to a different agent or augmenting with another medication is standard practice.

Abruptly stopping an antidepressant — especially paroxetine, venlafaxine, or duloxetine — can cause discontinuation syndrome: dizziness, nausea, brain zaps (electric shock sensations), irritability, and flu-like symptoms. This is not addiction; it's a physiological withdrawal effect. Gradual dose tapering over 2–4 weeks minimizes these symptoms.

If you or someone you know experiences worsening depression, suicidal thoughts, or unusual behavioral changes after starting an antidepressant, contact a healthcare provider immediately. Young adults (under 25) should be monitored closely during the first weeks of treatment. Never stop antidepressant medication abruptly without medical guidance.